Microbiome by Host Defense Mushrooms MycoBotanicals

POSSIBLY EFFECTIVE

• Constipation. Oral Bacillus coagulans seems to be beneficial for constipation. Details: Clinical research in individuals with mild intermittent constipation shows that taking B. coagulans SNZ 1969 (CTCBIO, Inc.) 1 billion colony-forming units (CFUs) daily for 8 weeks reduces colonic transit time, increases the number of weekly complete spontaneous bowel movements, and improves bowel discomfort when compared with placebo. Colonic transit time was reduced by at least 25% in 58% of patients taking B. coagulans, compared with 32% of patients taking placebo (107613). Other clinical research in patients with functional constipation shows that taking B. coagulans Unique IS2 (Unique Biotech Limited) 2 billion CFUs daily for 4 weeks modestly increases the number of bowel movements and reduces abdominal pain and pain with defecation when compared with placebo. Also, 98% of patients achieved normal stool consistency, compared with 74% of those taking placebo (107612). Adding lactulose 10 grams to this regimen increases stool frequency when compared with placebo, but not when compared with lactulose alone. However, normal stool consistency was achieved earlier and by more patients in those taking lactulose plus B. coagulans when compared with lactulose alone. The combination was also more beneficial for reducing defecation pain, abdominal pain, and sensations of incomplete evacuation (107614). Also, a small clinical study in adults with constipation-dominant functional bowel disorders shows that taking a specific supplement containing B. coagulans 1 billion CFUs twice daily for 4 weeks modestly improves abdominal pain and abdominal distention, as well as discomfort and effort during defecation, when compared with baseline (104232). However, the validity of the findings in this study is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Oral Bacillus coagulans seems to be beneficial for IBS. Details: Clinical research in adults with diarrhea-predominant IBS shows that taking B. coagulans daily for 56-90 days improves quality of life and decreases bloating, nausea, vomiting, abdominal pain, and stool frequency when compared with placebo. Improvements in headache, anxiety, and constipation have also been shown (92730,92735,92740,105169). In addition, meta-analyses show that taking B. coagulans reduces overall symptom, straining, and/or abdominal pain severity when compared with placebo (107594,110866). In one study, taking B. coagulans for 80 days resulted in no symptoms in 63% of individuals, compared with only 21% of those taking placebo (105169). Doses used in some of this clinical research have included a specific B. coagulans MTCC5856 product (Lactospore, Sabinsa Corporation) 2 billion colony-forming units (CFUs) daily for 90 days (92730), another specific B. coagulans product (GanedenBC30, Ganeden Biotech Inc.) 300 million to 2 billion CFUs daily for 8 weeks (92735,92740), B. coagulans LBSC (Advanced Enzyme Technologies Ltd.) 2 billion CFUs three times daily for 80 days (105169), or B. coagulans Unique IS2 2 billion CFUs daily for 8 weeks (110866). Other clinical research in adults with IBS shows that taking a specific combination product (Colinox, DMG Italia SRL) containing B. coagulans and simethicone after each meal three times daily for 4 weeks improves bloating and discomfort, but not pain, when compared with placebo (92726).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Although there has been interest in using oral Bacillus coagulans for antibiotic-associated diarrhea, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Athletic performance. It is unclear if oral Bacillus coagulans is beneficial for athletic performance. Details: A small clinical trial shows that taking an inactivated B. coagulans GBI-30, 6086 product (Staimune, Kerry, Inc) 1 billion cells daily for 2 weeks does not improve jump power or muscle endurance when compared with placebo (107610). This study might not have been adequately powered to detect differences between groups. A larger study in resistance-trained males shows that taking B. coagulans Unique IS-2 2 billion colony-forming units daily for 60 days in combination with 20 grams of an 80% whey protein concentrate modestly improves some measures of power and muscle strength when compared with taking whey protein alone. However, some measures of strength were not improved, and there was no effect on maximum oxygen consumption, muscle hypertrophy, or body composition (110878).
• Cancer. Although there has been interest in using oral Bacillus coagulans for cancer prevention, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Cirrhosis. Oral Bacillus coagulans has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with liver cirrhosis who are at increased risk for developing spontaneous bacterial peritonitis (SBP) shows that taking a combination of B. coagulans, Enterococcus faecalis, Clostridium butyricum, and Bacillus mesentericus three times daily, in conjunction with norfloxacin for 6 months, does not reduce the risk of developing SBP when compared with norfloxacin alone (92731).
• Clostridioides difficile infection. Although there has been interest in using oral Bacillus coagulans for C. difficile infection, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Depression. Although there has been interest in using oral Bacillus coagulans for depression, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Diabetes. Oral Bacillus coagulans has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with type 2 diabetes shows that taking B. coagulans GBI-30, 6086 (GanedenBC30) 100 billion CFUs, Lactobacillus acidophilus 1 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus 10 billion CFUs, and fructo-oligosaccharides 500 mg daily for 12 weeks modestly reduces fasting blood glucose and insulin and improves measures of insulin resistance when compared with placebo. There was no effect on plasma lipids (107731).
• Diarrhea. It is unclear if oral Bacillus coagulans is beneficial for acute diarrhea or diarrhea-dominant functional bowel disorders. Details: Clinical research in infants 6-24 months of age with acute diarrhea of various causes shows that taking B. coagulans 120 million colony-forming units (CFUs) twice daily for up to 5 days in conjunction with oral rehydration solution does not decrease duration, frequency, or volume of diarrhea when compared with oral rehydration solution and placebo (92738). However, a small clinical study in adults with acute diarrhea shows that taking a specific supplement (Lactic Acid Bacillus) containing B. coagulans 2 billion CFUs, three times daily for 7 days, reduces diarrhea and improves abdominal pain when compared with placebo (100853). Preliminary clinical research in adults with diarrhea-dominant functional bowel disorders shows that taking a specific supplement containing B. coagulans 1 billion CFUs twice daily for 4 weeks reduces abdominal pain, abdominal distention, discomfort and effort during defecation, and the number of stools classified as diarrhea when compared with baseline (104232). The validity of these findings is limited by the lack of a comparator group.
• Dyspepsia. It is unclear if oral Bacillus coagulans is beneficial for dyspepsia. Details: Several small studies show that B. coagulans can improve symptoms of dyspepsia (104231,104232,104233,107611). In one study, 1 billion colony-forming units (CFUs) were taken twice daily for 4 weeks, resulting in an improvement in abdominal pain and abdominal distention when compared with placebo (104232). Some studies have used B. coagulans in combination with other probiotics. In adults with functional dyspepsia, taking a combination of B. coagulans MY01 and Bacillus subtilis MY02 as 1.25 billion CFUs each twice daily for 8 weeks improves postprandial distress scores of at least 0.7 in 48% of patients, compared with only 20% of those taking placebo (107611). A small clinical study in older adults aged 55-75 years with indigestion, abdominal pain, and flatulence shows that taking a probiotic syrup containing B. coagulans 500 million CFUs with digestive enzymes (alpha amylase 25 mg, pepsin 10 mg, and lipase 1.5 mg) 5 mL twice daily for 5 days reduces symptoms of dyspepsia when compared with placebo (104233). Also, a small study in adults with non-specific gastrointestinal discomfort shows that taking a specific combination supplement (SNZ TriBac, Sanzyme Biologics) containing B. coagulans SNZ 1969, Bacillus clausii SNZ 1971, and B. subtilis SNZ 1972, 2 billion CFUs daily for 30 days, decreases self-reported symptoms of burping, belching, and sour taste when compared with placebo (104231). It is unclear if these effects are due to B. coagulans, other ingredients, or the combinations.
• Flatulence. It is unclear if oral Bacillus coagulans is beneficial for flatulence. Details: Clinical research in children aged 6-8 years shows that taking B. coagulans GBI-30, 6086 (GanedenBC30, Ganeden, Inc.) 1 billion colony-forming units (CFUs) daily for 3 months modestly decreases the incidence of flatulence when compared with taking placebo (107615). However, preliminary clinical research in patients with postprandial intestinal gas-related symptoms shows that taking a specific combination supplement (Digestive Advantage Gas Defense Formula, Ganeden Biotech) containing this same strain of B. coagulans and an enzyme blend daily for 4 weeks does not improve bloating or gas when compared with placebo (92736).
• Gingivitis. Although there has been interest in using oral Bacillus coagulans for gingivitis, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Helicobacter pylori. It is unclear if oral Bacillus coagulans is beneficial for H. pylori. Details: In patients with H. pylori, preliminary clinical research shows that taking B. coagulans (Donghai Pharmaceutical Co Ltd) 1050 mg three times daily for 8 weeks results in a 20% eradication rate 1-2 weeks after treatment. This was as effective as taking Clostridium butyricum 1050 mg twice daily, alone or in combination with B. coagulans (105168). This study is limited by lack of blinding and the lack of a placebo group. Also, it is unclear how B. coagulans compares to standard H. pylori eradication treatments.
• HIV/AIDS. Although there has been interest in using oral Bacillus coagulans for HIV/AIDS, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Hypercholesterolemia. Although there has been interest in using oral Bacillus coagulans for cholesterol reduction, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Inflammatory bowel disease (IBD). Although there has been interest in using oral Bacillus coagulans for IBD, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Necrotizing enterocolitis (NEC). It is unclear if oral Bacillus coagulans is beneficial or safe for NEC prevention. Details: Preliminary clinical research in infants with a gestational age of less than 33 weeks or a very low birth weight shows that taking B. coagulans 350 million colony-forming units daily until hospital discharge does not reduce the risk of NEC or death when compared with placebo. However, taking B. coagulans reduced the incidence of feeding intolerance in these newborns (92733). The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in very preterm or very low birth weight infants under 1000 grams (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral Bacillus coagulans is beneficial for NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that taking 1 capsule containing B. coagulans 1 billion colony-forming units plus 400 mg inulin for 8 weeks may be beneficial for treating inflammation associated with NAFLD when compared with placebo. However, this combination did not improve lipid profiles or glycemic indices. Inulin was used in this study as a prebiotic to ensure bacterial growth in the gut lumen (104230).
• Postoperative ileus. It is unclear if oral Bacillus coagulans is beneficial for postoperative ileus. Details: A small clinical study in patients undergoing gynecological laparoscopic surgery shows that taking B. coagulans TBC169 105 million or 175 million colony-forming units the night before surgery, and then every 8 hours starting 8 hours after surgery, reduces time to first flatus by up to 10 hours when compared with placebo. There were also modest reductions in the rates of postoperative gastrointestinal adverse events such as nausea, vomiting, distension, and ileus. However, there was no difference in time to first defecation or length of hospital stay (110879).
• Rheumatoid arthritis (RA). It is unclear if oral Bacillus coagulans is beneficial for RA. Details: Preliminary clinical research in adults with RA shows that taking B. coagulans GBI-30, 6086 (GanedenBC30, Ganeden Biotech Inc.) 2 billion colony-forming units daily for 60 days, in conjunction with standard therapy, reduces overall pain when compared with placebo. However, it does not reduce the number of painful or swollen joints or improve activities of daily living (92734).
• Rotaviral diarrhea. It is unclear if oral Bacillus coagulans is beneficial for rotaviral diarrhea. Details: Preliminary clinical research in newborns shows that taking B. coagulans 100 million colony-forming units daily for one year reduces the incidence of acute rotaviral diarrhea. Taking B. coagulans decreases the incidence of diarrheal episodes by around 5 per year and reduces duration of diarrhea by around 3 days per episode when compared with placebo. However, taking B. coagulans does not reduce the occurrence of mild to moderate dehydration (92729).
• Small intestinal bacterial overgrowth (SIBO). Oral Bacillus coagulans has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with SIBO who were previously treated for 3 weeks with broad spectrum antibiotics shows that taking a specific probiotic product (Lactol, Bioplus Life Sciences Pvt. Ltd.) containing B. coagulans spores and fructo-oligosaccharides twice daily on 15 days per month for 6 months, in conjunction with minocycline, modestly decreases stomach pain and flatulence (91145).
• Travelers' diarrhea. Although there has been interest in using oral Bacillus coagulans for travelers' diarrhea, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Upper respiratory tract infection (URTI). It is unclear if oral Bacillus coagulans is beneficial for URTI prevention. Details: Clinical research in children aged 6-8 years shows that taking B. coagulans GBI-30, 6086 (GanedenBC30, Ganeden, Inc.) 1 billion colony-forming units (CFUs) daily for 3 months modestly decreases the incidence of some URTI symptoms, including nasal congestion, bloody nasal mucus, itchy nose, and hoarseness, but not others such as dry cough and sore throat, when compared with placebo (107615). More evidence is needed to rate Bacillus coagulans for these uses.

(Read more about BACILLUS COAGULANS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical burdock for acne, there is insufficient reliable information about the clinical effects of burdock for this purpose.
• Aging skin. It is unclear if topical burdock is beneficial for reducing wrinkles. Details: A very small study in females aged 39-65 years shows that applying an emulsion containing burdock fruit extract 1.2% to the face twice daily for 4 weeks slightly reduces skin wrinkles around the eyes when compared with placebo (37420).
• Atopic dermatitis (eczema). Although there is interest in using topical burdock for eczema, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Breast cancer. Oral burdock root has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Population research in breast cancer patients has found that using a specific product containing burdock root, sheep sorrel, slippery elm bark, and Indian rhubarb (Essiac, Resperin Canada Limited) is not associated with improved quality of life when compared with no intervention (37419).
• Common cold. Although there is interest in using oral burdock for symptoms of the common cold, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Diabetes. Although there is interest in using oral burdock for diabetes, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Diverticulitis. It is unclear if oral burdock is beneficial in patients with diverticulitis. Details: A small open-label clinical study in patients with colonic diverticulitis shows that taking burdock tea (Ajikan, Co., Ltd.) providing 1.5 grams three times daily for a median of 26 months is associated with an acute diverticulitis recurrence rate of 11%, compared with 32% of those not taking burdock tea. Furthermore, the recurrence-free duration was increased by about 14 months. However, taking burdock tea for a median of 16 months does not prevent colonic diverticular bleeding recurrence (102696).
• Dry skin. Although there is interest in using topical burdock for dry skin, there is insufficient reliable information about the clinical effects of burdock for this purpose.
• Gout. Although there is interest in using oral burdock for gout, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Hepatitis. Although there is interest in using oral burdock for hepatitis, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Metabolic syndrome. It is unclear if oral burdock is beneficial in patients with metabolic syndrome. Details: A very small clinical study in patients with metabolic syndrome shows that drinking burdock extract 100 mL three times daily after meals for 16 weeks does not reduce body weight, abdominal fat, blood pressure, lipid levels, or glucose when compared with baseline or control (105667).
• Obesity. Although there is interest in using oral burdock for obesity, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Urinary tract infections (UTIs). Although there is interest in using oral burdock for UTI, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Vaginitis. Topical burdock has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in adults and children with vaginitis has found that applying a specific solution containing burdock, chamomile, and aloe (Zelesse, ITF Research Pharma S.L.U., Alcobendas) to the vaginal area once or twice daily for 5-20 days is associated with moderate improvements in symptoms such as pruritus, erythema, and discharge when compared with baseline (102695,102697). The validity of this finding is limited by its observational nature and the lack of a control group. More evidence is needed to rate burdock for these uses.

(Read more about BURDOCK)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Small clinical studies suggest that oral FOS may modestly improve symptoms in patients with constipation when used in combination with probiotics. The benefits of FOS when used alone are unclear. Details: Most clinical research has evaluated the use of FOS for constipation in conjunction with probiotics. Preliminary clinical research in adults with chronic functional constipation shows that taking an unspecified dose of a specific product (Hexbio) consisting of FOS, Lactobacillus acidophilus, Lacticaseibacillus casei, Lactococcus lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium infantis orally twice daily for 7 days increases defecation frequency by 3-fold when compared with placebo. Taking this product also improved patient reported symptoms of straining, lumpy hard stools, and incomplete evacuation sensations (90266). Other clinical research in adult females with constipation shows that taking a different product (Lactofos, SKL Functional Nutrition Ltda.) containing FOS 6 grams and Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium lactis 0.1-1 billion colony-forming units each, orally twice daily for 30 days, modestly increases the frequency of evacuation and decreases constipation severity when compared with placebo (90300). It is unclear if these effects are due to FOS, other ingredients, or the combination. In children aged 4-8 years with functional constipation, preliminary clinical research shows that taking a mixture of FOS 0.45 grams and polydextrose 4.17 grams orally daily for 45 days improves the weekly frequency of bowel movements, clinical manifestations of constipation, and quality of stool type when compared with baseline (106482). It is unclear if these effects are due to FOS, polydextrose, or the combination. Additionally, the validity of these findings is limited by the lack of a comparator group. Clinical research evaluating the use of FOS alone is limited. Preliminary clinical research in elderly males shows that taking FOS alone 3-10 grams daily for 30 days increases the frequency of defecation by 1.5-fold when compared with baseline (8505). The validity of this study is limited by the lack of a comparator group. In non-breastfeeding infants 6-24 months of age with constipation, preliminary clinical research shows that fortifying formula or milk with FOS daily for 4 weeks increases the frequency of soft stools by 33% and decreases the frequency of straining by 55% when compared with placebo. However, the use of FOS did not increase the percentage of infants who achieved normal bowel pattern. The daily dose of FOS was 6 grams for infants 6-8.9 kg, 9 grams for infants 9-11.9 kg, and 12 grams for infants over 12 kg (98651).
• Diabetes. Oral FOS has only been evaluated in combination with probiotics; its effect when used alone is unclear. Details: Preliminary clinical research in adults with type 2 diabetes shows that taking a combination product containing FOS 500 mg, Bacillus coagulans 100 billion spores, Lacticaseibacillus rhamnosus 10 billion colony-forming units (CFUs), and Lactobacillus acidophilus 1 billion CFUs once daily for 12 weeks reduces fasting blood glucose by 17 mg/dL, compared with an increase of 3 mg/dL with placebo. However, taking this product did not affect body weight, waist circumference, or cholesterol levels. It is unclear if this effect is due to FOS, other ingredients, or the combination (107731).
• Hematopoietic stem cell transplant (HSCT). It is unclear if oral FOS is beneficial in patients undergoing HSCT. Details: Preliminary clinical research in patients undergoing an allogeneic HSCT shows that taking a specific oral FOS supplement, (Fibrulose F97, Cosucra Groupe) 5-15 grams daily for 21 days, beginning 5 days before transplant, does not reduce acute graft-versus-host disease, blood stream infections, or Clostridioides difficile infections or improve overall survival when compared with control (107931). However, this study may have been inadequately powered to detect a difference between groups.
• Hypercholesterolemia. Although there has been interest in using oral FOS for hypercholesterolemia, there is insufficient reliable information about the clinical effects of FOS for this purpose.
• Obesity. Although there has been interest in using oral FOS for obesity, there is insufficient reliable information about the clinical effects of FOS for this purpose.
• Osteoporosis. Oral FOS has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in postmenopausal adults shows that taking a specific FOS product (NutraFlora, Ingredion Inc.) 3.2 grams plus calcium 800 mg daily for 24 months reduces the decline in total-body bone mineral density (BMD) when compared with calcium alone, but not when compared with a maltodextrin control. In a subgroup of patients with osteopenia, this combination reduced the decline in BMD in the lumbar vertebrae when compared with calcium alone or a maltodextrin control (94931).
• Travelers' diarrhea. It is unclear if oral FOS is beneficial for preventing traveler's' diarrhea. Details: Preliminary clinical research shows that taking FOS 10 grams orally daily for 4 weeks, starting 2 weeks before traveling to a medium- to high-risk destination, does not reduce the incidence of travelers' diarrhea when compared with placebo (10373). However, the study may have been inadequately powered to detect a difference between groups. More evidence is needed to rate FOS for these uses.

(Read more about FRUCTO-OLIGOSACCHARIDES (FOS))

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral lion's mane mushroom is beneficial in patients with Alzheimer disease. Details: Preliminary clinical research in patients over 50 years of age with mild Alzheimer disease shows that taking lion's mane mushroom mycelia (standardized to contain 5 mg/gram of erinacrine A) 1.05 grams daily for 49 weeks improves performance of activities of daily living when compared with placebo. It also improves scores on the Mini-Mental State Examination when compared with baseline (105546). The validity of these findings is reduced by the lack of an intention to treat analysis, and the comparison of some outcomes to baseline instead of placebo.
• Anxiety. Although there is interest in using oral lion's mane mushroom for anxiety, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Athletic performance. Although there is interest in using oral lion's mane mushroom for improving athletic performance, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this purpose.
• Cancer. Although there is interest in using oral lion's mane mushroom for cancer, there is insufficient reliable information about the clinical effects of lions mane mushroom for this purpose.
• Cognitive function. Small clinical trials suggest that lion's mane mushroom does not improve cognitive function. Details: A small clinical trial shows that taking lion's mane mushroom 3.2 grams daily for 12 weeks does not improve most measures of cognitive function when compared with placebo in middle aged to older adults (101770). Additional clinical research in younger adults shows that taking lion's mane mushroom 10 grams daily for 4 weeks does not improve markers of cognition during a period of exercise-induced fatigue when compared with taking placebo. The lion's mane product is 50% dried mushroom and 50% extract (111932). These studies were small and may have been underpowered to detect differences.
• Cognitive impairment. It is unclear if oral lion's mane mushroom is beneficial in patients with mild cognitive impairment. Details: One clinical study in Japanese patients aged 50-80 years old with mild cognitive impairment shows that taking lion's mane mushroom powder 1 gram three times daily for 16 weeks increases cognitive function when compared with placebo. However, cognitive function regresses within 4 weeks of treatment termination (91999).
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral lion's mane mushroom for COVID-19, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this purpose.
• Dementia. Although there is interest in using oral lion's mane mushroom for dementia, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Depression. It is unclear if oral lion's mane mushroom is beneficial in patients with depression. Details: Preliminary clinical research in perimenopausal patients without a formal diagnosis of depression shows that eating 4 cookies daily, each containing 0.5 grams powdered lion's mane mushroom, for 4 weeks is similarly effective to placebo cookies for reducing scores on a depression scale (105547).
• Diabetes. Although there is interest in using oral lion's mane mushroom for diabetes, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Gastritis. It is unclear if oral lion's mane mushroom is beneficial in patients with chronic atrophic gastritis. Details: Preliminary clinical research in patients with chronic atrophic gastritis shows that taking lion's mane mushroom (unknown dose) before meals daily for 3 months improves upper abdominal pain in about 27% more patients, improves dyspepsia in about 39% more patients, and reduces inflammatory infiltration in about 23% more patients when compared with placebo (92630).
• Hyperlipidemia. Although there is interest in using oral lion's mane mushroom for hyperlipidemia, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Memory. Although there is interest in using oral lion's mane mushroom for memory, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this purpose.
• Multiple sclerosis (MS). Although there is interest in using oral lion's mane mushroom for MS, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Obesity. Although there is interest in using oral lion's mane mushroom for obesity, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Parkinson disease. Although there is interest in using oral lion's mane mushroom for Parkinson disease, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Peptic ulcers. Although there is interest in using oral lion's mane mushroom for peptic ulcers, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition.
• Wound healing. Although there is interest in using topical lion's mane mushroom for wound healing, there is insufficient reliable information about the clinical effects of lion's mane mushroom for this condition. More evidence is needed to rate lion's mane mushroom for these uses.

(Read more about LION'S MANE MUSHROOM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• ACE inhibitor-induced cough. It is unclear if oral marshmallow root is beneficial in patients with cough due to ACE inhibitors. Details: A small clinical study in patients with ACE inhibitor-induced cough shows that taking marshmallow root 40 mg (20 drops) three times daily for 4 weeks improves cough when compared to baseline (62027). The validity of this finding is limited by the lack of a control group.
• Atopic dermatitis (eczema). It is unclear if topical marshmallow is beneficial in children with eczema. Details: A very small clinical study in children ages 3 months to 12 years with a recent diagnosis of mild to moderate eczema shows that applying a marshmallow 1% ointment twice daily for 1 week and then three times weekly for 3 weeks seems to reduce symptoms, as measured on the SCORing Atopic Dermatitis (SCORAD) scale, when compared with applying hydrocortisone 1% ointment (105437). This finding is limited by the large number of drop-outs due to non-compliance, most of which were in the marshmallow group.
• Breast engorgement. It is unclear if topical marshmallow is beneficial in women with this condition. Details: A small clinical study in breastfeeding women with breast engorgement shows that applying a compress containing 40-50 mL of a solution made from marshmallow leaves and stems 3 times daily for 2 days in conjunction with standard treatment improves patient-reported breast engorgement scores when compared with standard treatment alone. Standard treatment consisted of massage and alternating warm and cold compresses before and after breastfeeding (92845).
• Constipation. Although there is interest in using oral marshmallow for constipation, there is insufficient reliable information about the clinical effects of marshmallow for this condition.
• Cough. Although there is interest in using oral marshmallow for cough, there is insufficient reliable information about the clinical effects of marshmallow for this condition.
• Diarrhea. Although there is interest in using oral marshmallow for diarrhea, there is insufficient reliable information about the clinical effects of marshmallow for this condition.
• Fever. It is unclear if topical marshmallow is beneficial for pediatric fever. Details: A moderate-sized clinical study in children aged 6 months-10 years with fever receiving rectal acetaminophen shows that applying marshmallow extract body wash and lukewarm water reduces the time to defervescence by 8 minutes when compared with lukewarm water alone, but does not improve the change in body temperature, number of acetaminophen doses given, or incidence of fever recurrence (112375). However, the interpretation of these findings is limited to patients without fevers greater than 40 degrees Celsius or history of febrile seizures since these patients were not studied.
• Leishmania lesions. Topical marshmallow has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research suggests that the topical application of an herbal extract containing a combination of marshmallow and Althaea rosa to affected areas for 5 days can help promote curing of Leishmania lesions (62020).
• Respiratory tract infections. Although there is interest in using oral marshmallow for respiratory tract infections, there is insufficient reliable information about the clinical effects of marshmallow for this condition.
• Vaginal candidiasis. It is unclear if vaginal marshmallow is beneficial for vulvovaginal candidiasis. Details: A small clinical study in adults with vulvovaginal candidiasis shows that applying a vaginal cream comprised of marshmallow extract 4% and clotrimazole 1% daily for 7 days improves itching, dyspareunia, and dysuria at 7 days when compared with clotrimazole 1% alone. At 30 days, the marshmallow intervention also results in fewer positive yeast cultures and sustained reduction in itching (112371). However, the validity of these results is limited by significant differences between groups at baseline for dyspareunia and dysuria, and lack of adjustment for multiple comparisons which can increase false positive findings. Additionally, all primary outcomes were patient-reported.
• Venous leg ulcers. Although there is interest in using topical marshmallow for venous leg ulcers, there is insufficient reliable information about the clinical effects of marshmallow for this condition.
• Wounds. Although there is interest in using topical marshmallow for wounds, there is insufficient reliable information about the clinical effects of marshmallow for this condition. More evidence is needed to rate marshmallow for these uses.

(Read more about MARSHMALLOW)

POSSIBLY INEFFECTIVE

• Hyperlipidemia. Preliminary clinical studies show that oral reishi mushroom does not improve lipid levels in patients with hyperlipidemia or type 2 diabetes. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not significantly improve the lipid profile in patients with hyperlipidemia (70776). Also, a meta-analysis shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce total cholesterol or low-density lipoprotein (LDL) cholesterol in patients with type 2 diabetes (91435).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral reishi mushroom for aging, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Altitude sickness. Although there has been interest in using oral reishi mushroom for altitude sickness, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Alzheimer disease. A small clinical study suggests that oral reishi mushroom does not improve Alzheimer disease symptoms. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking reishi mushroom powder 1000 mg three times daily for 6 weeks does not improve memory, language skills, or quality of life when compared with placebo (97942).
• Asthma. Although there has been interest in using oral reishi mushroom for asthma, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Benign prostatic hyperplasia (BPH). Preliminary clinical research suggests that oral reishi mushroom extract can help reduce some lower urinary tract symptoms in patients with BPH. Details: Clinical research in patients with mild to moderate lower urinary tract symptoms (LUTS) associated with BPH, urinary incontinence, overactive bladder, or other conditions, shows that taking reishi mushroom extract 6 mg orally once daily for up to 12 weeks moderately improves total symptom severity measured on the International Prostate Symptom Score (IPSS) scale, when compared with placebo (91436,91437). A higher dose of 60 mg daily is not more effective than the 6 mg dose, and a lower dose of 0.6 mg daily is not more effective than placebo (91437). Reishi mushroom extract does not improve peak urine flow rate, residual urine volume, prostate volume, or quality of life when compared with placebo (91436,91437). The relevance of these results is unclear since not all of the patients with LUTS had BPH.
• Bronchitis. Although there has been interest in using oral reishi mushroom for bronchitis, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Cancer. It is unclear if oral reishi mushroom is beneficial when used in conjunction with chemotherapy. Details: A meta-analysis of 9 clinical trials using various reishi mushroom products in combination with chemotherapy found that complete and partial responses increased by 30% with combination therapy when compared with chemotherapy alone. However, there was no difference in overall survival (102915). The reliability and applicability of these results are unclear since the trials looked at several different types of cancer, used varying doses and durations of therapy, and were all conducted in China or other Asian countries.
• Cancer-related fatigue. It is unclear if oral reishi mushroom is beneficial in patients with breast cancer and fatigue. Details: Results from a small clinical study in breast cancer patients show that taking reishi mushroom powder 1000 mg orally three times daily for 4 weeks can improve cancer-related fatigue when compared with placebo (91438). However, it is not clear if the improvement is clinically meaningful.
• Cardiovascular disease (CVD). It is unclear if oral reishi mushroom is beneficial for reducing CVD risk factors. Details: A meta-analysis of 5 low-quality studies in adults with diabetes shows that taking reishi mushroom 1400-3000 mg daily for 12-16 weeks does not reduce CVD risk factors, including total and low-density lipoprotein (LDL) cholesterol, triglycerides, blood pressure, and body mass index, when compared with placebo (91435).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral reishi mushroom for CFS, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Chronic kidney disease (CKD). Although there has been interest in using oral reishi mushroom for CKD, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Colorectal adenoma. Limited clinical research suggests that oral reishi mushroom extract may be beneficial for reducing colorectal adenoma size. Details: Preliminary clinical research in patients with colorectal adenomas shows that taking reishi mushroom extract 1500 mg orally in two divided doses daily for 12 months reduces the number and size of adenomas when compared with no treatment (70774).
• Coronary heart disease (CHD). It is unclear if oral reishi mushroom is beneficial for CHD. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces symptoms of CHD, such as chest pain, palpitations, and shortness of breath, in a greater percentage of patients when compared with placebo (70800).
• Diabetes. Evidence on the use of oral reishi mushroom in patients with type 2 diabetes is conflicting. Details: A meta-analysis of clinical research in patients with type 2 diabetes shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce glycated hemoglobin (HbA1c) or plasma lipids (91435). However, one preliminary clinical study in patients with type 2 diabetes shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg three times daily for 12 weeks reduces HbA1c, but not fasting blood glucose, when compared with placebo (70801).
• Fibromyalgia. It is unclear if oral reishi mushroom is beneficial for fibromyalgia. Details: A small clinical trial in patients with fibromyalgia shows that taking reishi mushroom (MundoReishi Salud S.L.) powder 3 grams twice daily for 6 weeks does not improve mood, quality of life, anthropometric measures, blood pressure, or glycemic or lipid parameters when compared with placebo (108309,108310). However, the study may have been underpowered to detect any differences between groups.
• Genital herpes. Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent genital herpes shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by 6 days when compared with previous outbreaks (91434).
• Gulf war syndrome. It is unclear if oral reishi mushroom is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in adults with Gulf war syndrome shows that taking reishi mushroom extract (JHS Natural Products, Mushroom Science) 1600 mg in two divided doses daily for 30 days does not improve symptoms when compared with placebo. Also, symptoms modestly worsened after an additional 30 days of treatment at a dose of 3200 mg daily (108311).
• Hepatitis B. One small clinical study suggests that a specific reishi mushroom extract may reduce hepatitis B activity and improve liver function. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces levels of hepatitis B viral DNA and hepatitis B surface antigen, which are markers of hepatitis B activity, and normalizes aminotransferase levels in a greater percentage of patients when compared with placebo (70799).
• Herpes labialis (cold sores). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent herpes labialis shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by almost 4 days when compared with previous outbreaks (91434).
• Herpes zoster (shingles). Although there has been interest in using oral reishi mushroom for herpes zoster, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Human papillomavirus (HPV). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oral HPV shows that taking a combination of reishi and coriolus mushroom powders, 400 mg orally daily for 2 months, clears HPV in 88% of patients when compared with baseline (91433). The validity of this finding is limited by the lack of a comparator group.
• Hypertension. Limited research suggests that oral reishi mushroom may be beneficial in some types of hypertension. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not lower blood pressure in patients with hypertension (70776). However, in other clinical research, taking reishi mushroom extract 330-1440 mg daily for 1-6 months reduces blood pressure in patients with stage II or essential hypertension, but not in those with mild hypertension or diabetes (70786,70802,91435).
• Influenza. Although there has been interest in using reishi mushroom for influenza, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Insomnia. Although there has been interest in using reishi mushroom for insomnia, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Lung cancer. Small clinical studies suggest that oral reishi mushroom does not reduce the size of lung tumors. Details: A meta-analysis of preliminary clinical research shows that taking reishi mushroom does not reduce the size of lung tumors. However, it may stimulate immune function and improve quality of life in lung cancer patients when compared with control (70779).
• Peptic ulcers. Although there has been interest in using oral reishi mushroom for peptic ulcers, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Rheumatoid arthritis (RA). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with active RA who are taking disease-modifying antirheumatic drugs shows that taking reishi mushroom extract 4 grams in combination with San Miao San (containing 2.4 grams each of atractylodes, phellodendron, and Achyranthes bidentata) daily for 24 weeks does not increase the percentage of patients achieving a 20% response based on the American College of Rheumatology (ACR) criteria or modify blood markers of disease and inflammation when compared with placebo (70767).
• Stress. Although there has been interest in using oral reishi mushroom for stress, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose. More evidence is needed to rate reishi mushroom for these uses.

(Read more about REISHI MUSHROOM)

POSSIBLY EFFECTIVE

• Cancer. Taking PSK, a constituent of turkey tail mushroom, as an adjunct to standard cancer therapy may improve response rates and survival in some patients with cancer. Very limited data suggests that whole turkey tail mushroom is not beneficial. Details: The PSK constituent of turkey tail mushroom has been used as an adjunct to standard cancer therapy in Japan for several decades, in doses ranging from 1 to 3.6 grams daily (94076). It has been used in a dose of 3 grams daily for 24-36 months for breast (1648,1650,1654,1656), colorectal (1657,1660,70165,70167,70168,70171,70173,70174,70176,70190)(94076), esophageal (1649), gastric (1640,1651,1652,1657,1658,1659,1660,70161,70170,70175)(70179,70181,70183,70186,70189,70191,70194,70198), hepatic (1655,70188), and lung cancers (1653,70180,70184), as well as for leukemia (70200,70206). It has also been used in a dose of 1 gram daily for up to 72 months for colorectal cancer (94076), 1 gram three times daily for 1 month for nasopharyngeal cancer (1661,70195), and 2 grams/m2 per day in 3 divided doses, rotating in cycles with chemotherapy, for gastric cancer (1659,70194,70195). A meta-analysis of 13 clinical trials including over 2500 patients with esophageal, gastric, colon, rectal, breast, or nasopharyngeal cancer, shows that taking PSK in addition to conventional therapy reduces 5-year mortality by 9% when compared with conventional therapy alone. When individual cancer types are considered, the benefit of PSK is most evident in patients with breast, gastric, colon, or rectal cancer (94076). Another meta-analysis of 14 clinical trials shows that taking PSK, polysaccharide peptide (PSP), or turkey tail mushroom in combination with chemotherapy is associated with a 17% lower risk of mortality in some, but not all, types of cancer when compared with chemotherapy alone. However, overall there was no difference in relapse-free survival or total clinical efficacy, defined as complete responses plus partial responses (102915). The reliability and relevance of these meta-analyses is unclear since the trials looked at several different types of cancer, used varying doses and durations of therapy with different turkey tail mushroom extracts, and were all conducted in China or other Asian countries. Research on the use of whole turkey tail mushroom rather than the constituent PSK for treating cancer is limited. A small clinical study in 15 patients with inoperable hepatocellular carcinoma shows that taking turkey tail mushroom 2.4 grams daily for 6-12 weeks does not improve time to progression, progression-free survival, overall survival, or quality of life when compared with placebo (96568). However, this study was likely underpowered to detect any differences.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cervical dysplasia. Intravaginal turkey tail mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A specific vaginal gel (Papilocare, Procare Health) containing turkey tail mushroom, neem, carboxymethyl-beta-glucan, hyaluronic acid, gotu kola, aloe, and alpha-glucan oligosaccharide has been examined in preliminary clinical and observational research in patients with human papillomavirus (HPV)-related cervical lesions. One clinical study shows that topical application for 6 months is associated with a normal Pap smear in 85% of patients, compared with 65% of those receiving only regular monitoring. Benefits were greatest in high-risk patients (108305). In patients over 40 years of age, treatment with this gel resulted in a normal Pap smear in 92% of patients, compared with 50% of those receiving only regular monitoring (111905). Both studies also showed improvements in cervical re-epithelization and HPV clearance (108305,111905). Observational research has also been conducted. One observational study in patients with high-risk HPV infection has found that using this same product is associated with 4.8-, 2.3-, and 5.1-fold increased odds of HPV DNA clearance, remission at colposcopy, and remission with cytology at 6 months, respectively, when compared with untreated patients (108306). In another observational study, using this product for 6 or 12 months is associated with repair of cervical low-grade lesions and a normalized cytology and colposcopy in about 75% of patients. HPV clearance was achieved in 71.6% of patients (111904). Doses of gel administration have varied. The gel is usually applied once daily for 21 days, followed by 7 days with no treatment, and then alternate days for up to 2-12 months (108305,108306,111904,111905). It is occasionally applied once daily for 21 days, followed by 7 days with no treatment, repeated for 3 months, and then alternated days for 3 months (108305).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral turkey tail mushroom for CFS, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Genital herpes. Although there has been interest in using oral turkey tail mushroom for genital herpes, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Hepatitis. Although there has been interest in using oral turkey tail mushroom for hepatitis, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Muscle strength. Although there has been interest in using oral turkey tail mushroom for muscle strength, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Tinea corporis. Although there has been interest in using oral turkey tail mushroom for tinea corporis, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral turkey tail mushroom for URTI, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral turkey tail mushroom for UTIs, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose. More evidence is needed to rate turkey tail mushroom for these uses.

(Read more about TURKEY TAIL MUSHROOM)

POSSIBLY SAFE ...when taken orally and appropriately. Bacillus coagulans spores in doses up to 6 billion colony-forming units (CFUs) daily have been used with apparent safety in clinical studies for up to 3 months (92726,92730,92734,92735,92736,92739,92740,104231,105169)(107611,107612,107614). Lower doses of B. coagulans up to 100 million CFUs daily have been used with apparent safety in clinical studies for up to one year (92738). There is insufficient reliable information available about the safety of non-viable, heat-killed B. coagulans formulations when used orally.

CHILDREN: POSSIBLY SAFE
when taken orally and appropriately. Bacillus coagulans spores in doses up to 100 million colony-forming units (CFUs) daily have been used with apparent safety in clinical studies in infants of most ages for up to one year (92729,92733,92738) and in doses of one billion CFUs in children aged 6-8 years for 3 months (107615). There is insufficient reliable information available about the safety of Bacillus coagulans in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BACILLUS COAGULANS)

LIKELY SAFE ...when used in amounts commonly found in foods (12659,12660). Burdock root is commonly eaten as a vegetable (37422,92153,92154)

POSSIBLY SAFE ...when used topically, short-term. An emulsion containing burdock fruit extract 1.2% has been safely applied to the face twice daily for 4 weeks (37420). There is insufficient reliable information available about the safety of burdock when used orally in supplemental doses.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BURDOCK)

POSSIBLY SAFE ...when used orally and appropriately, alone or in combination with probiotics, in doses up to 30 grams daily for up to 4 weeks (741,745,8505,90266,107729,107931). ...when a specific FOS product (NutraFlora, Ingredion Inc.) is used orally in combination with calcium at doses up to 3.2 grams daily for up to 24 months (94931).

CHILDREN: POSSIBLY SAFE
when short-chain FOS are included in approved infant formulas for healthy term infants at a level of up to 4 grams/L or 1 gram/kg daily (94929,94930,98651).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about FRUCTO-OLIGOSACCHARIDES (FOS))

LIKELY SAFE ...when marshmallow root and leaf are used in amounts commonly found in foods. Marshmallow root has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

POSSIBLY SAFE ...when marshmallow root and leaf are used orally in medicinal amounts (4,12). ...when used topically (4,62020). There is insufficient reliable information available about the safety of marshmallow flower.

PREGNANCY AND LACTATION:
Insufficient reliable information available.

(Read more about MARSHMALLOW)

POSSIBLY SAFE ...when an extract of reishi mushroom is used orally and appropriately for up to one year (12,5485,70767,70774,70786,70799,70800,70801,70802). ...when whole powdered reishi mushroom is used orally and appropriately for up to 16 weeks (70776,70799,70800,70801,91433,91435,91436,91437,108309).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using

(Read more about REISHI MUSHROOM)

LIKELY SAFE ...when turkey tail mushroom is used orally and appropriately (5477). ...when polysaccharide krestin (PSK) and polysaccharide peptide (PSP) isolates of turkey tail mushroom are used orally and appropriately (1635,1636,1640,1641,1648,1649,1650,1651,1652,1653,1654) (1655,1656,1657,1658,1659,1660,1661,1662,70167,70168,70171,70188,70200,94076). There is insufficient reliable information available about the safety of turkey tail mushroom when used topically or intravaginally.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about TURKEY TAIL MUSHROOM)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking antibiotics with Bacillus coagulans might decrease the effectiveness of B. coagulans.  Details B. coagulans preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. coagulans preparations by at least two hours.

(Read more about BACILLUS COAGULANS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking burdock with anticoagulant or antiplatelet drugs might increase the risk of bleeding.  Details In vitro research shows that lignans from burdock reduce rabbit platelet aggregation by inhibiting platelet activating factor (12619). This interaction has not been reported in humans.

(Read more about BURDOCK)

(Read more about FRUCTO-OLIGOSACCHARIDES (FOS))

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, lion's mane mushroom may increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.  Details In vitro research suggests that lion's mane mushroom extracts can inhibit platelet aggregation (92619).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, lion's mane mushroom may have additive effects when used with antidiabetes drugs.  Details Animal research suggests that an aqueous extract of lion's mane mushroom can reduce serum glucose and increase serum insulin (91996).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of lion's mane mushroom might interfere with immunosuppressive therapy.  Details In animal and in vitro research, lion's mane mushroom polysaccharides stimulate the immune system (91933,111933).

(Read more about LION'S MANE MUSHROOM)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, marshmallow flower might have antiplatelet effects.  Details Animal research suggests that marshmallow flower extract has antiplatelet effects (92846). However, the root and leaf of marshmallow, not the flower, are the plant parts most commonly found in dietary supplements. Theoretically, use of marshmallow flower with anticoagulant/antiplatelet drugs can have additive effects, and might increase the risk for bleeding in some patients.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, due to potential diuretic effects, marshmallow might reduce excretion and increase levels of lithium.  Details Marshmallow is thought to have diuretic properties. To avoid lithium toxicity, the dose of lithium might need to be decreased when used with marshmallow.

ORAL DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, mucilage in marshmallow might impair absorption of oral drugs.  Details Marshmallow contains mucilage which can affect oral drug absorption (1,11,12,19). To avoid changes in absorption, take marshmallow 30-60 minutes after oral medications.

(Read more about MARSHMALLOW)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of reishi mushroom might increase the risk of bleeding.  Details A dose of 1.5 grams daily of reishi mushroom does not seem to decrease platelet aggregation, but a higher dose of 3 grams daily does (5476,13235).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, reishi mushroom might have additive effects with antidiabetes drugs.  Details Animal research suggests that reishi mushroom decreases blood sugar (70769). However, in patients with type 2 diabetes, taking reishi mushroom does not reduce fasting glucose levels, and its effects on glycated hemoglobin are inconsistent (70801,91435).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of reishi mushroom with antihypertensive drugs might increase the risk of hypotension.  Details Reishi mushroom has shown hypotensive activity in animal research (5488,70784). Clinical evidence suggests that reishi mushroom reduces blood pressure in some, but not all, patients with hypertension (70786,70802).

(Read more about REISHI MUSHROOM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking turkey tail mushroom with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research suggests that turkey tail mushroom and a polysaccharide component can have hypoglycemic effects (108307,111907).

CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, the polysaccharide peptide (PSP) component of turkey tail mushroom might increase exposure to cyclophosphamide.  Details Some animal research shows that the PSP component of turkey tail mushroom can increase the area under the concentration-time curve (AUC) of cyclophosphamide by 44% to 50% and the half-life by 34% to 43% (96569). This interaction could potentially increase the effects and adverse effects of cyclophosphamide. However, it is not known whether PSP affects the levels of the active metabolites of cyclophosphamide that are responsible for its clinical activity.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, the polysaccharide peptide (PSP) component of turkey tail mushroom might inhibit CYP2C9.  Details Laboratory research suggests that the PSP component of turkey tail mushroom dose-dependently inhibits CYP2C9 (94075). Theoretically, taking PSP with drugs metabolized by CYP2C9 might increase drug levels and the risk of adverse effects. However, this has not been reported in humans.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, the polysaccharide peptide (PSP) component of turkey tail mushroom might interfere with the absorption of tamoxifen.  Details Animal research suggests that PSP increases the time to reach maximum concentration of a single dose of tamoxifen by about 9.5 hours, or 228%. When repeated doses of tamoxifen were given, the time to reach maximum concentration was increased by about 5.6 hours, or 93%. However, PSP did not affect the maximum concentration or the area under the curve of tamoxifen (108308).

(Read more about TURKEY TAIL MUSHROOM)

General ...Orally, Bacillus coagulans is well tolerated.
Serious Adverse Effects (Rare):
Orally: There is concern that probiotics may cause infections in some people.

Immunologic ...Since many probiotic preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. Bacteremia and sepsis have been reported in patients with indwelling or central venous catheters or patients who are severely ill and/or immunocompromised, including preterm infants, that were using probiotic products (4380,8561,13008,13070,90298,102416,103444,105138,105140,105141)(107543,107597,107599,111610,111612,111613,111850,111852,111853). However, reports of pathogenic colonization in relatively healthy patients with intact immune systems who do not have indwelling or central venous catheters are extremely rare (4380,4389,4390,4391,4393,4398,105139,107543,107545,107546,107547).

(Read more about BACILLUS COAGULANS)

General ...Orally, burdock is well tolerated when consumed as a food. Although a thorough evaluation of safety outcomes is lacking, there has been long-standing historical use of burdock with few noted adverse effects.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions, including contact dermatitis and anaphylaxis.

Dermatologic ...Contact dermatitis has been reported secondary to burdock, especially after prolonged use of the root oil (37422). There are cases of allergic dermatitis secondary to using burdock plasters. Two males and a 14 year-old female developed erythematous and vesicular, pruritic, and exudative reactions in areas corresponding to the application of burdock root plasters (12667). Reactions occurred up to 7 days after initial use. Patch testing was positive for burdock sensitivity in all three patients and was nonreactive in matched controls.

Hematologic ...In one case report, a 38-year-old female developed immune-mediated thrombocytopenia after consuming a "cleansing" tea containing unknown amounts of burdock and yellow dock. The patient presented with bruising, mild weakness, and fatigue, which started 2-3 days after consuming the tea, and was found to have a platelet count of 5,000 per mcL. Symptoms resolved after platelet transfusion and treatment with oral dexamethasone (108971). It is unclear if these effects were caused by burdock, yellow dock, the combination, or other contributing factors.

Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing burdock and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to burdock, other ingredients, or the combination.

Immunologic ...There is one case of anaphylactic shock secondary to eating boiled burdock. One hour after eating boiled burdock the patient presented with redness over the entire body and dyspnea. He was found to have low blood pressure and was treated with subcutaneous epinephrine 1 mg and intravenous lactated ringer's solution containing hydrocortisone 100 mg and dexamethasone 8 mg. The cause of anaphylactic shock was attributed to allergenicity to burdock based on positive skin prick test results. Previously, the patient had experienced urticaria after eating boiled burdock (12660).

Neurologic/CNS ...Anticholinergic reactions including dry mouth, dizziness, blurred vision, weakness, dilated pupils, inability to urinate, and bradycardia have been reported following the consumption of burdock products (12662,37421,37431,37434,37435). However, these anticholinergic reactions are believed result from contamination of burdock with belladonna alkaloids. Burdock itself does not contain atropine or other constituents that would be responsible for these reactions.

(Read more about BURDOCK)

General ...Orally, FOS are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, flatulence.

Gastrointestinal ...Orally, FOS may cause flatulence, belching, abdominal pain, intestinal sounds, constipation, and bloating. These symptoms can occur commonly in some patients, but are generally mild at doses under 10 grams per day (745,750,8509,98651,107931). However, a meta-analysis of 8 small clinical studies shows that taking FOS at doses ranging from 2.5 grams to 15 grams daily for up to 8 weeks does not increase the rate of abdominal pain, bloating, flatulence, or intestinal sounds when compared with control groups (110710).

(Read more about FRUCTO-OLIGOSACCHARIDES (FOS))

General ...Orally, lion's mane mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, nausea, skin rash.

Dermatologic ...Orally, lion's mane mushroom may cause skin rash (105546).

Gastrointestinal ...Orally, lion's mane mushroom may cause gastrointestinal discomfort and nausea (91999,105546).

(Read more about LION'S MANE MUSHROOM)

General ...Orally and topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about MARSHMALLOW)

General ...Orally, reishi mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, dry mouth, itching, nausea, rash, and stomach upset.

Dermatologic ...Orally, reishi mushroom can cause itching, rash, and other skin reactions (12,5479).

Gastrointestinal ...Orally, reishi mushroom can cause dryness of the mouth, throat, or nasal cavity, nausea, stomach upset, and, more rarely, diarrhea (12,70779,91438,108309).

Hematologic ...Orally, reishi mushroom can cause nosebleed and bloody stools (12,91438).

Hepatic ...One case of hepatotoxicity and one case of fatal fulminant hepatitis have been reported in patients who had used reishi mushroom powder for 1-2 months (70766). There is a case report of a 61-year-old male with hypereosinophilia associated with hepatic nodules following the use of reishi mushroom powder for about 2 months. Symptoms resolved after discontinuation of the product. Although these side effects were thought to be associated with the use of reishi mushroom powder, it is unclear if other factors played a role. The patient had been taking tegafur, gimeracil, and oteracil potassium for about 4 months following anterior resection for rectal adenocarcinoma but discontinued these agents and initiated reishi mushroom due to liver injury (108312).

Neurologic/CNS ...Orally, reishi mushroom can cause dizziness (91438). Other rare symptoms include insomnia and headache (70776,70779).

Pulmonary/Respiratory ...Respiratory allergy to reishi spores can occur (12,5479). Sore throat and runny nose have also been reported (70776,91438).

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General ...Orally, turkey tail mushroom and its PSK component are generally well tolerated. There have been reports of gastrointestinal side effects, hematological abnormalities, liver dysfunction, and palpitations, but these are in patients who received PSK in addition to standard chemotherapy. It is not known if these are due to PSK, the chemotherapy, or both.

Cardiovascular ...Palpitations have occurred when PSK is taken with standard chemotherapy for cancer (1657). It is not clear if this is due to PSK, the chemotherapy, or both.

Dermatologic ...Pigmentation of the nails and erythema have occurred when PSK is taken with standard chemotherapy (1657,1660,70175,94076). It is not clear if this is due to PSK, the chemotherapy, or both.
Intravaginally, a specific gel (Papilocare, Procare Health) containing turkey tail mushroom with neem, carboxymethyl-beta-glucan, hyaluronic acid, gotu kola, aloe, and alpha-glucan oligosaccharide has been reported to cause vulvovaginal stinging, burning, itching, and candidiasis (108305,111904). The specific role of turkey tail mushroom is unclear.

Gastrointestinal ...Nausea, vomiting, appetite loss, stomach discomfort, diarrhea, constipation, and gastric ulcer have occurred when PSK is taken with standard chemotherapy for cancer (1651,1657,70175,70201,94076). However, one study reported a decreased incidence of gastrointestinal side effects when PSK was taken with chemotherapy (70188,70197).

Hematologic ...Leukopenia, thrombocytopenia, and albuminuria have occurred when PSK is taken with standard chemotherapy (1651,1657,70175,70201,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

Hepatic ...Elevated liver enzymes, liver function impairment, and hepatotoxicity have occurred when PSK is taken with standard chemotherapy (1651,1657,70175,70201,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

Musculoskeletal ...Malaise and fatigue have occurred when PSK is taken with standard chemotherapy (1657,1660,70175,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

Pulmonary/Respiratory ...Coughing has occurred when PSK is taken with standard chemotherapy (1657,1660,70175,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

(Read more about TURKEY TAIL MUSHROOM)